Dispensing assembly with interchangeable cartridge pumps

ABSTRACT

This invention describes a cartridge pump and dispensing assembly for applications where cartridges containing liquid reagents are interchanged often. The cartridge pump comprises a reagent reservoir which directly empties into a metering chamber. A valve is at each end of the metering chamber. The two valves are aligned in the same direction so as to allow unidirectional liquid flow. The metering chamber is made of a compressible material, such as flexible tubing, so that when an external compression is applied to the chamber, the liquid contained therein is forcibly expelled. As the compression is removed, the metering chamber resumes its former shape and draws liquid into the chamber from the reagent reservoir. A dispensing assembly with electromechanical actuators for compression of the metering chamber and a means for sensing the amount of liquid contained within the reagent reservoir are also shown.

RELATED APPLICATIONS

This application is a Continuation-in-Part of U.S. Ser. No. 08/251,597,filed May 31, 1994, now U.S. Pat. No. 5,645,114 which is aContinuation-in-Part of application Ser. No. 07/881,397 which was filedon May 11, 1992, now U.S. Pat. No. 5,316,452. The contents of all of theabove noted related applications are incorporated herein by reference intheir entirety.

BACKGROUND OF THE INVENTION

This invention relates to a pump mechanism for dispensing small aliquotsof a fluid, such as a biological reagent. It may serve as part of anapparatus which dispenses a plurality of reagents to be dispensed insmall volumes.

Current methods for dispensing reagents generally use pumps whichrequire the priming of tubing lines leading into and out of a pump. Whenthe pumping is finished, the tubing lines must be flushed before adifferent reagent can be pumped, lest cross-contamination of reagentsoccur. Because of the need for priming and clearing tubing lines, suchtypes of pumps are not easily interchangeable.

Pumping systems using a syringe housing ("syringe pumps") are well knownto those in the field. The syringe is first filled with a liquid. Theliquid can then be accurately dispensed by applying a precise pressureon the plunger, usually by an electromechanical actuator. The distancethat the plunger is depressed directly controls the amount of fluid tobe dispensed. Such syringe pumps have two advantages: 1) the absence oftubing lines leading into and out of a pump which must be primed andflushed, and 2) a separation of the wetted components from theelectromechanical controlling elements.

Such syringe pumps are useful in situations where repetitive dispensingof precise amounts of liquid are required. A drawback of such syringepumps is that interchanging syringes on a single electromechanicalactuator requires that the actuator mechanism be realigned with theposition of the syringe plunger that is being inserted. In circumstanceswhere the syringes need to be changed often in order to change thedispensed reagent, the need for repetitive manual intervention to alignthe electromechanical actuator with the position of the syringe plungeris a disadvantage. This disadvantage will be more acutely felt in adispensing instrument with many electromechanical actuators.

SUMMARY OF THE INVENTION

In accordance with an aspect of the present invention, a pump cartridgecomprises a reagent reservoir for containing a liquid. The reservoir hasa liquid flow outlet at the bottom thereof. A metering chamber isdirectly connected to the liquid flow outlet of the reagent reservoir.The metering chamber comprises a compressible housing having anoncompressed shape. A one-way inlet valve and a one-way outlet valveare provided at respective ends of the compressible housing and arealigned in the same direction to allow unidirectional flow from thereservoir through the housing. The compressible housing may becompressed for the unidirectional ejection of a volume of liquid fromthe metering chamber. The compressible housing returns to thenoncompressed shape after cessation of compression to draw an additionalvolume of liquid into the metering chamber.

A cartridge pump in accordance with the present invention may be used asa component of a movable platform containing a plurality ofelectromechanical actuators. In this manner, any desired liquid reagentcontained in any of the cartridges can be dispensed at any locationunderneath the platform's reach. Alternatively, the present inventionincludes a rotor containing reagents and a rotor containing slides thatrotate on the same axis. A single actuator is located on a stationenabling the slides to be accessed by the reagents. At the end of theworking session, the cartridges can be easily replaced with differentcartridges using the same electromechanical actuators without the needfor aligning electromechanical actuators with the cartridges. Thisaspect increases the versatility of the dispensing instrument as awhole.

In a dispensing assembly, a pump cartridge frame may hold the pumpcartridge in a fixed position with respect to an actuator capable ofcompressing the compressible housing of the pump cartridge. Preferably,the actuator is an electromechanical actuator. The dispensing assemblymay be mounted on a moveable platform for dispensing various reagents invarious sample cells. In one embodiment, a plurality ofelectromechanical actuators are positioned adjacent to a plurality ofreceptacles on the frame into which a plurality of pump cartridges canbe fit.

The cartridge may have one or more ridges extending outwardly from itsexternal surface to serve as keys in grooves in a supporting frame.Cartridges may be coded by the circumferential positions of ridges toassure that cartridges containing particular reagents are inserted inappropriate locations in the frame.

According to another aspect of the invention, a dispensing assemblycomprises an assembly base and a slide rotor adapted to carry aplurality of slides holding tissue samples. This slide rotor is capableof rotating on the assembly base. Further, a reagent rotor adapted tocarry a plurality of different reagents sits above the slide rotor andis also capable of rotating on the assembly base.

In preferred embodiments, slide frames are provided for holding theslides in the slide rotor. The slide frames are radially insertable intothe slide rotor. These slide frames themselves comprise a slide framebase adapted to support a plurality of slides and containing resistiveheating units for heating each one of these slides. A thermocouple canalso be provided to detect the temperature of the slides as heated bythe resistive heating units. A slide frame housing is adapted tosealably fit over the slide frame base to create cavities over each ofthe slides and place each of these slides in fluid isolation from eachother.

The reagent rotor carries at least one pump cartridge frame thatcomprises a plurality of receptacles for receiving a plurality ofcartridge pumps. These cartridge pumps comprise a reservoir forcontaining a reagent, a resilient metering chamber in fluidcommunication with an outlet of the reservoir and a one way inlet valveand one way outlet valve at each end of the resilient metering chamber.

The dispensing assembly further comprises a dispensing stationpositioned adjacent to each of the slide rotor and the reagent rotor.This dispensing station comprises an actuator adapted to deform theresilient metering chamber in a cartridge pump so that a volume ofreagent contained in that cartridge pump is ejected into a slideunderneath the cartridge pump held by the slide rotor. This dispensingstation also includes a plurality of pressurized rinse bottles and rinsetubes that extend from the rinse station above the slides held by theslide rotor. As such, they can convey rinsing solutions by the openingof pinch valves to the slides underneath the ends of the rinse tubes.Still further, the dispensing station includes a vacuum bottle andvacuum hose that is extendable into a cavity above the slides on theslide rotor to enable removal of rinse solutions covering the slides.

According to another aspect, the reagent reservoir of the cartridgepumps may contain a plunger above the liquid in the reagent reservoir.The plunger is capable of moving within the reservoir as liquid is drawnout of the reservoir through the liquid flow outlet. Preferably, theplunger has a frictional force against the inner wall of the reservoirwhich is greater than the gravity pressure of the liquid in thereservoir in order to prevent spontaneous dripping of the liquid out ofthe outlet valve. Alternatively, the outlet valve in its normally closedposition may itself have an opening pressure which is greater than thegravity pressure applied by the liquid in the reservoir. Alternatives tothe plunger include a one-way valve at the top of the reservoir, arolling diaphragm at the top of the reservoir and a small aperture atthe top of the reservoir.

To reduce the flow velocity of liquid during ejection, a nozzle with aninner diameter which is greater than the opening diameter of the outletvalve may be positioned below the outlet valve.

To absorb some of the initial force upon impact of the actuator againstthe tubing, the actuator may be a compressible piston hammer mounted ona piston arm.

The interchangeable pump cartridge of the present invention can beaccepted into a dispensing assembly with an electromechanical actuatorregardless of the amount of liquid in the cartridge reservoir. Thecartridge maintains a separation of the wetted and electromechanicalcomponents and does not require priming of tubing lines before and afterpumping. Moreover, it may be produced inexpensively and therefore can bedisposed of when the reagent in the cartridge is exhausted. As a furtheradvantage over syringe pumps, the cartridge pump of the presentinvention allows for dispersing of relatively small, precisely meteredvolumes.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, features and advantages of theinvention will be apparent from the following more particulardescription of preferred embodiments of the invention, as illustrated inthe accompanying drawings in which like reference characters refer tothe same parts throughout the different views. The drawings are notnecessarily to scale, emphasis instead being placed upon illustratingthe principles of the invention.

FIG. 1 is a cross-sectional view of the pump cartridge and dispensingactuator mounted on a frame.

FIG. 2 is a perspective view of the pump cartridge reservoir.

FIG. 3 is a view from above of the pump cartridge.

FIG. 4 is a view from above of a plurality of pump cartridges mounted ona first embodiment dispensing assembly including a rectangular frame andchassis of an X-Y axis robot.

FIG. 5 is a perspective view of a dispensing assembly of a secondembodiment of the invention.

FIG. 6 is a top view of a slide frame for providing five sealed cavitiesabove five different slides holding tissue samples.

FIG. 7 is a top view of a slide frame base.

FIG. 8 is a top view of a slide frame housing.

FIG. 9 is a side cross-sectional view showing the dispensing actuator ofthe dispensing station and an exemplary cartridge pump being engaged bythe dispensing actuator.

FIG. 10 is a side cross-sectional view of a rinse device housed in thedispensing station.

FIGS. 11A and 11B are side cross-sectional views of a vacuum hose andtransport mechanism for removing rinse and reagent from slides containedon the slide rotor.

FIGS. 12-14 are cross-sectional views of the uppermost portion of thecartridge reservoir, demonstrating alternative constructions.

FIGS. 15 and 16 are longitudinal sectional views of an alternativedispenser pump cartridge embodying the invention.

FIG. 17 is a longitudinal sectional view of the metering chamber tubingof the embodiment of FIGS. 15 and 16.

FIG. 18 is a cross-sectional view of a valve needle and plate used inthe embodiment of FIGS. 15 and 16.

DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT

Referring to FIG. 1, the cartridge pump CP comprises a pump cartridgereservoir 1 in the shape of a cylindrical barrel. The cartridgereservoir 1 has a lower outlet 11 which is directly connected to ametering chamber comprised of a segment of compressible tubing 2, aninlet valve 3, and an outlet valve 4. The distance between the inletvalve 3 and the outlet valve 4, and the inner diameter of the tubing 2defines a volume which can be filled with a liquid. A nozzle 5 is placedbelow the outlet valve 4 for the purpose of decreasing the flow velocityof the liquid. The cartridge reservoir contains a volume of liquid 12which is sealed from above by a sliding plunger 6. The cartridgereservoir 1, inlet valve 3, outlet valve 4, plunger 6, metering chamber2, and nozzle 5 are the components of the cartridge pump CP.

In a first embodiment of a dispensing assembly, the cartridge pump CPrests on a rectangular frame 7 which can be made of plastic. A singlerectangular frame 7 can hold a plurality of cartridge pumps CP. Therectangular frame 7 can be removed from the chassis 8 by simply liftingthe frame, thereby lifting all the cartridge pumps with it. In thismanner, the wetted components can be easily separated from theelectromechanical components.

The first embodiment dispensing assembly further includes dispensingactuators DA. Each dispensing actuator DA comprises a solenoid 9, arm22, and rubber hammer 1. When an electrical current is applied to thesolenoid 9, the arm 22 extends forcefully, thereby pressing the rubberhammer 10 against the outer wall of the metering chamber tubing 2. Thisaction deforms the tubing, causing the compressible tubing to assume acompressed shape 2a. Since the total volume inside the metering chamberbetween the valves 3 and 4 is decreased, a volume of liquid is expelledin the direction defined by the valves 3 and 4. In FIG. 1, the valvesare shown as allowing fluid in the downward direction only. Since thediameter of the outlet valve 4 leaflets is comparatively narrow relativeto the diameter of the tubing 2, the fluid has a high flow velocity.This results in a forceful squirting of the liquid. This aspect is oftenundesirable, since it may lead to splattering of the liquid if theobject surface of the fluid is situated immediately below. Therefore,the nozzle 5 is placed below the outlet valve 4. The nozzle has an innerdiameter greater than the diameter of the outlet valve 4 leaflets. Thisaspect causes the high velocity fluid to first accumulate in the spaceabove and within the inner aspect of the nozzle. The liquid thus exitsthe nozzle 5 at a slower velocity, ideally in a dropwise manner.

The rubber hammer 10 is also compressible in order to further decreasethe flow velocity of the liquid. Most solenoids tend to extend suddenlyand forcefully. This results in a very rapid compression of the tubing2. In order to decrease this rate of compression, the solenoid arm isfitted with a compressible rubber hammer 10 which absorbs some of theinitial force upon impact with the tubing 2.

The tubing 2 can be made of silicone rubber, vinyl, polyurethane,flexible polyvinyl chloride (PVC) or other synthetic or naturalresilient elastomers. Such types of tubing are commonly used forperistaltic pumps. The valves can be obtained from Vernay Laboratories,Inc., Yellow Springs, Ohio, 45387 (part #VL 743-102).

When the electrical current is removed from the solenoid 9, the arm 22and rubber hammer 10 is retracted from the surface of the tubing 2. Thetubing in the compressed position 2a thereby reverts back to its nativeposition 2 because of the resiliency of the tubing. The reversion of thetubing to its native position results in a negative pressure beingcreated within the metering chamber, causing liquid 12 to be drawn fromthe pump reservoir 1 into the metering chamber. The metering chamber istherefore automatically primed for the next pump cycle.

Referring to FIG. 2, the outer aspect of the pump cartridge reservoir 1has longitudinal ridges 13. These ridges fit into grooves in the frame7, see FIG. 1, in a lock and key fashion. Different cartridges aremanufactured with different patterns of ridges in order to identify thecontents. In this manner, any particular cartridge will fit only into aposition of the frame with a corresponding pattern of grooves. Thisfeature will prevent the possibility of the operator placing thecartridge in an unintended position of the frame.

Referring to FIG. 3, this shows the variety of possible positions forridges 13 on the outer surface of the pump cartridge reservoir 1.

Referring to FIG. 4, this shows the first embodiment of the dispensingassembly comprising a rectangular frame 7 having plurality of slots 14for cartridge pumps in position on the chassis 8 a different dispensingactuator DA being associated with each cartridge pump CP. The chassis ismounted on a pair of cylindrical bars 15. In this case one of the barsis threaded and attached to a motor 16. Alternatively, a cable drive maybe provided. The motor can be a conventional stepping motor or servomotor and driven by a computer-generated signal through an electronicinterface.

FIG. 5 shows a second embodiment 500 of a dispensing assembly inperspective. Generally, the dispensing assembly 500 comprises asubstantially circular assembly base 502, a slide rotor 504 rotatable onthe assembly base 502, a reagent rotor 506 also rotatable on theassembly base, and a dispensing station 508.

The slide rotor 504 is driven to rotate by a servo motor (not shown) andcarries ten slide frames 510 that are radially asserted into anddetachable from it. A top view of single slide frame 510 is shown inFIG. 6. Here, a different slide holding a tissue sample is held in eachslide position 512a-512e. The slide frame 510 comprises a slide framebase 514 shown in FIG. 7. The slide frame base includes a plurality ofheated areas 516 which underlie each of the slide positions 512a-512eand incorporate resistive heating elements, not shown. The heatingelements are integrally formed in the slide frame base 514. Electricityfor powering the elements is provided into the slide frame 510 from theassembly base 502 via first and second contacts. Further, third andfourth contacts 520 enable temperature sensing of the heated areas viathermocouples also integrally formed in the slide frame base 514.Adapted to overlay the slide frame base is a slide frame housing 522.FIG. 8 is a top view of the slide frame housing 522 showing essentiallya rigid plastic or metal frame 524 with five oval holes 526a-526ecorresponding to each of the slide positions 512a-512e. A silicon rubbergasket 528 is also provided under the plastic frame 524. Returning toFIG. 6, the slide frame housing 522, including the gasket 528 andplastic frame 524, is bolted onto the slide frame base 514 by two Allenbolts 530 to provide individual sealed cavities approximately 0.2-0.4inches deep over each tissue sample slide placed at each of the slidepositions 512a-512e. As a result, a total of 3 ml of reagents and/orrinses can be placed in contact with the tissue samples of each one ofthe slides but a maximum quantity of 2 ml is preferable. Since thesilicone gasket 528 is compressed by-the plastic frame 522 against theslide frame base 514, the cavities over each of the frame positions aremutually sealed from each other.

Returning to FIG. 5, above the slide rotor 504 is a non-rotating slidecover 532. This disk-like structure rides above the slide rotor 504 butdoes not turn with the slide rotor. Basically, it forms a cover for allof the tissue samples held in each of the slide frames 510 so thatevaporation of reagents or rinses contained on the slides can beinhibited and also so that environmental contamination of the tissuesamples is prevented.

Positioned above the slide rotor 504 is the reagent rotor 506. Thisreagent rotor 506 is similarly adapted to rotate on the assembly base502 and is driven by another servo motor (not shown) so that the reagentrotor 506 and slide rotor 504 can rotate independently from each other.The reagent rotor 506 is adapted to carry up to ten arcuate cartridgeframes 534. These arcuate cartridge frames are detachable from thereagent rotor 506 and can be selectively attached at any one of the tenpossible points of connection. Each arcuate cartridge frame 534 iscapable of carrying five of the reagent cartridge pumps CP. A crosssectional view illustrating the arcuate cartridge frame as shown in FIG.9. As illustrated, the reagent cartridge pump CP is verticallyinsertable down into a slot 536 in the arcuate cartridge frame 534 sothat the nozzle tip 538 extends down below the cartridge frame and themeter chamber tubing 2 is exposed. The arcuate cartridge frame 534including any cartridge pumps CP is then slidably insertable onto thereagent rotor 506.

Generally, the dispensing station 508 comprises a dispensing actuator DAfor engaging the meter chamber tubing 2 of any one of the reagentcartridge pumps CP in any slot in any one of the arcuate cartridgeframes 534. Further, the dispensing station 508 includes rinse bottles540 that can supply rinses into any one of the slides on any one of theslide frames 510 via rinse tubes 542, and a rinse removal vacuum 544including a vacuum tube that is extendable down into any one of thecavities in the slide frames 510 to remove rinse or reagent.

Specifically, the dispensing station 508 includes a station frame thathas a front wall 546 generally following the curvature of the assemblybase 502. The station frame also includes a horizontal top wall 548continuous with the front wall 546 and from which rinse bottles 540 arehung. The front wall 546 of the station housing supports a singledispensing actuator DA. As best shown in connection with FIG. 9, thedispensing actuator DA includes a solenoid or linear stepping motor 9,an arm 22, and a compressible rubber hammer 10 as described inconnection with the dispensing actuator illustrated in FIG. 1. Use of alinear stepping motor instead of a solenoid somewhat negates thenecessity of the rubber hammer being highly compressible since the rateof extension of linear stepping motors can be controlled to a slowspeed. Because only a single dispensing actuator is required in thesecond embodiment, more expensive alternatives such as the linearstepping motor are preferable. As another possible alternative, thereciprocating hammer of the dispensing actuator could take the form of acam, driven by a rotary motor, that engages the compressible tubing sothat rotation of the cam will deform the compressible tubing.

Upon actuation of the solenoid 9, the rubber hammer 10 extends outwardlyto engage the compressible tubing 2 of the particular cartridge pump CPthat has been rotated into position in front of the dispensing actuatorDA on the reagent rotor 504. The liquid dispensed from the pumpcartridge CP by the action of the dispensing actuator DA falls downthrough a hole 550 formed in the slide cover 532 into the particularmedical slide that has been brought into position in front of thedispensing actuator DA by the rotation of the slide rotor 504. In thisway, any one of fifty slides, which the slide rotor 504 is capable ofcarrying, can be accessed and treated with any one of fifty differentreagents that the reagent rotor 506 is capable of carrying in thecartridge pumps CP by properly rotating both the reagent rotor and theslide rotor. By this method both the reagent cartridge pump CP carryingthe desired reagent and the slide which the operator intends to receivethis reagent are brought to circumferential position of the dispensingactuator DA.

The dispensing station 508 also carries up to eight different rinsesthat can be delivered through rinse tubes 542 to any one of the slidesheld on the slide rotor 504. As shown in FIG. 10, the rinse bottles 540are screwed into a female threaded cap 552 secured to the underside ofthe horizontal top wall 546 of the station frame. Compressed air is froma compressor 554 is provided into each one of the rinse bottles 540. Thepressure above the rinse then enables the rinse to be forced out throughthe dip tube 556 through rinse hose 558 when a pinch valve 560 isopened. Depending on the length of time that the pinch valve is opened,a predetermined amount of rinse can be provided out through the rinsetube 542 into the particular medical slide that has been broughtunderneath the rinse tube end 562 by the rotation of the slide rotor.Eight different rinse tubes 542 corresponding to each rinse bottle 540and each controlled by a separate pinch valve. Eight holes are providedin the slide cover 532 underneath the ends of the rinse tubes 542 sothat the rinse can reach the slides.

Returning to FIG. 5, also provided on the vertical wall 544 of thestation housing is an extendable vacuum hose 544. As more completelyshown in cross section in FIG. 11A, the vacuum hose 544 is supported bya hose transport mechanism 570 that allows the vacuum hose 544 to beextended down into a cavity of a slide frame 510 to remove any rinse andreagent covering the tissue sample of the slide. Specifically, thesuction is created by a partial vacuum generated in vacuum bottle 572 bya compressor, not shown. Consequently, the rinse and reagent is suckedin through the vacuum hose 544 and into the vacuum bottle when thevacuum hose transport mechanism 570 brings the vacuum hose end incontact with the rinse and/or reagent in cavity of the slide frame 510.

The vacuum hose transport mechanism comprises a motor 574. Areciprocating link 576 is attached to a crank arm 575 so that therotation of the motor 574 causes the reciprocating link 576 to traversein a vertical direction. A bottom portion of the reciprocating link 576is connected to a lever 578 that is pivotally attached to the stationframe. The other end of this lever is connected to a vacuum hose clamp580 that is connected via to pivot arms 582 to a plate 584 rigidlyattached to the station frame. The net effect of these connections isthat when the motor 574 is rotated, the slide arm 576 descends in thevertical direction. Thus, the lever 578 is pivoted clockwise around itsfulcrum causing the hose clamp 580 to pivot up and away on the two pivotarms 582 from the slide as shown in FIG. 11b. The motor is automaticallyturned off as the slide reaches its two extreme ends of movement by thecontact of the electrical terminals 584 of the slide to the contactplates 586 connected to the station frame.

A microprocessor, not shown, controls the entire dispensing assembly500. That is, an operator programs the microprocessor with theinformation such as the location of reagents on the reagent rotor andthe location of slides on the slide rotor. The operator then programsthe particular histochemical protocol to be performed on the tissuesamples. Variables in these protocols can include the particular reagentused on the tissue sample, the time that the tissue sample is allowed toreact with the reagent, whether the tissue sample is then heated toexposed or develop the tissue sample, the rinse that is then used todeactivate the reagent, followed by the subsequent removal of the rinseand reagent to allow subsequent exposure to a possibly differentreagent. The dispensing assembly enables complete random access, i.e.any reagent to any slide in any sequence.

An important aspect of the above-described invention is its ability toretain the fluid until such time as the solenoid hammer 10 presses onthe metering chamber tubing 2. As will be noted from FIG. 1, bothone-way valves 3 and 4 are aligned in the same direction, allowing onlydownward flow. It was found during construction that using valves with alow opening ("cracking") pressure resulted in the liquid dripping out ofthe nozzle. There are two solutions to this problem. The most obvious isto use valves with an opening pressure greater than the pressure head ofliquid. In this manner, the outlet valve 4 will not allow fluid exituntil a certain minimum force is applied which is greater than thepressure head of the standing liquid.

A second alternative to prevent spontaneous dripping of the liquid outof the outlet valve 4 is to use a plunger 6 with an amount of frictionagainst the inner surface of the reservoir 1 greater than the gravitypressure of the liquid 12. An additional advantage of the plunger 6 isthat it prevents spillage of the liquid 12 from the top of the reservoir1 (which would likely occur if the reservoir were left open from above).In this manner, the plunger will not be drawn downwards inside thereservoir merely by the weight of the liquid. However, when the meteringchamber is emptied and a small amount of liquid is drawn from thereservoir 1 to refill the metering chamber, the plunger's friction tothe reservoir wall is overcome. The plunger 6 thereby moves downward adistance proportional to the volume of liquid expelled. We have found ituseful to apply a thin coat of a lubricant such as petroleum jelly toensure that the plunger 6 moves smoothly downward within the reservoir.

Any combination of valve opening pressure and plunger friction may beused to prevent dripping, but given the low opening pressure typicallyfound in valves of the type used, friction greater than gravity pressureof the liquid is preferred.

FIG. 12 shows another alternative construction of the cartridge top.Instead of using a plunger, a one-way valve 17 is placed at the top ofthe reservoir 1. The valve 17 has an opening pressure greater than thegravity pressure of the liquid within the reservoir. This third valve 17is aligned in the same direction as the metering chamber valves 3 and 4.This allows the entrance of air into the reservoir as liquid is removed.In this case, cracking pressure of any or all of the three valves 3, 4and 17 prevents spontaneous dripping from the outlet valve.Additionally, the valve 17 prevents spillage of the contents of thereservoir.

FIG. 13 shows another alternative construction for the top of thecartridge. A rolling diaphragm cover 18 is mounted at the top of thereservoir 1 and is drawn into the reservoir as the liquid is used up.This construction prevents spillage of the liquid 12 as well as providesa seal to prevent air entry. The rolling diaphragm can be made of anythin flexible elastomer such as natural rubber. The top of the rollingdiaphragm can be sealed to the reservoir wall 1 by stretching thediaphragm over the reservoir, with an adhesive or by heat sealing.

FIG. 14 demonstrates a third alternative construction. The top of thereservoir is closed, except for a small aperture 19 for the entrance ofair. The diameter of the aperture at the top of the reservoir can besufficiently small to effectively prevent accidental spillage of theliquid contents of the cartridge but still allow air entry as liquid isdispensed from the cartridge.

A fluid level sensor may be provided adjacent to the cartridgereservoir. For example, a shaft can be connected to the top of theplunger. The shaft can be designed with a shape such that as it is drawninto the cartridge reservoir, it can optically or electrically open orclose a circuit at a certain depth within the cartridge reservoir. Inthis manner, the shaft connected to the plunger can signal to a computerthe depth of entry into the cartridge reservoir. The depth of entrywould therefore be directly proportional to the amount of liquidremaining in the cartridge reservoir. Such an arrangement provides anautomatic means for sensing the amount of liquid remaining inside thereservoir.

A variety of different configurations for the dispensing actuators DAmay be used to apply pressure on the metering chamber tubing. Although apush-type of actuator DA is shown in FIG. 1, a rotary or pull-type couldalso be used with slight modifications to the design, as would beobvious so as to apply a pressure on the metering chamber tubing.Additionally, a solenoid valve could also be used to control pressure toa pneumatic cylinder whose piston rod is the actuator. Alternatively, apiezoelectric transducer may apply the pressure to the metering chambertubing.

An alternative dispensing pump cartridge is illustrated in FIGS. 15through 18. As in prior embodiments, the pump cartridge includes aliquid reservoir, in this case a flexible plastic bag 612 within a rigidhousing 614. FIGS. 15 and 16 show the housing and longitudinal sectionin views from the front and side. FIG. 16 shows the bag collapsed, itbeing recognized that it would expand to fill the volume within thehousing when filled with liquid. The open end of the reservoir bag 612fits snugly about an inlet end of a metering chamber tube 616 and isclamped and thus sealed to the tube by a plate 618 which also serves asa closure to the housing 614. As in prior embodiments, the tube 616 isadapted to be compressed by an actuator 10 to expel liquid through aone-way outlet valve 620. When the actuator 10 is then released, thewall of the tube 616 returns to its native position and thus createsnegative pressure within the metering chamber. That negative pressuredraws liquid from the liquid reservoir 612 through a one-way inlet valve622 into the metering chamber. Significantly, both valves are passivecheck valves, the dispensing being controlled by the single actuator 10.Mechanical complexity is avoided, and a cartridge may be readilyreplaced by dropping the cartridge into place with the tubing of themetering chamber positioned adjacent to the actuator 10.

The novel valves of this embodiment provide relatively large sealingforces to minimize leakage while still requiring very small pressuredifferential to open. Further, the flow path below the sealing surfaceof the outlet valve 620 is minimal, thus minimizing any caking ofreagent on flow surfaces. As in the embodiment of FIG. 1, the one-wayvalves are formed from flexible leaflets. However, in this embodiment aleaflet takes the form of a flat membrane having a central pinhole whichseals against a pointed protrusion. Specifically, in the outlet valve68, a membrane 624 is preferably formed of unitary plastic with the tube616. A disk 626 (FIG. 18) snaps between the membrane 624 and a moldedflange 628 within the metering chamber tube 616 (FIG. 17). A valveneedle 630 extends as a protrusion from the plate 626. The needle may bea separate piece press fit into the plate 626 as illustrated in FIG. 18,or it may be molded as a unitary piece with the plate 626. The tip ofthe valve needle 630 extends into the pinhole 632 within the membrane624, thus flexing the membrane in an outward direction. Due to theresiliency of the membrane, it presses back against the valve needle 630with a sealing force sufficient to withstand the pressure head of theliquid contained within the metering chamber tube 616.

The plate 626 has a hole 634 to allow fluid flow therethrough. When thetube 616 is compressed by the actuator 10, the increased pressure withinthe metering chamber is applied across the entire upper surface area ofthe membrane 624 such that a low level of pressure is required to causethe membrane to flex and break the seal about the valve needle 630.Liquid then flows through the hole 634 and the pinhole 632.

The inlet valve 622 is similarly constructed with a membrane 636 andvalve needle plate 638 retained within the internal flanges 640 and 642in the metering chamber tube 616. With the low pressure differentialrequired to open the valve, the tube 616 is able to return to its nativeposition and draw liquid into the metering chamber from the reservoir612. On the other hand, when the actuator 10 compresses the meteringchamber 616, the force against the membrane 636 is sufficient to sealthat membrane against the valve needle of the plate 638.

While this invention has been particularly shown and described withreferences to preferred embodiments thereof, it will be understood bythose skilled in the art that various changes in form and details may bemade therein without departing from the spirit and scope of theinvention as defined by the appended claims. For example, the pump isoperable with the metering chamber positioned above the reservoir.Disclosure Document No. 252981 filed May 10, 1990 at the U.S. Patent andTrademark Office shows details of a potential system embodying thepresent invention.

What is claimed is:
 1. A method of performing reactions on a pluralityof specimens mounted on microscope slides comprising:providing a reagentdispensing assembly over a microscope slide carrier, the reagentdispensing assembly comprising:a reagent reservoir; and a reagentmetering chamber comprising a compressible elastomeric housing suspendedfrom the reagent reservoir to receive liquid through an inlet from thereservoir and unidirectional check valves at an inlet and an outlet,respectively, of the compressible elastomeric housing; positioning aplurality of microscope slides on the slide carrier; moving the reagentdispensing assembly and slide carrier relative to each other to positionthe reagent dispensing assembly over a selected microscope slide;compressing the compressible elastomeric housing of the reagent meteringchamber to eject reagent through the outlet check valve onto theselected slide; and relaxing the reagent metering chamber to drawreagent into the reagent metering chamber from the reagent reservoir. 2.A method as claimed in claim 1 wherein the slide carrier is a rotatingslide carousel.
 3. A method as claimed in claim 2 further comprisingproviding a plurality of reagent dispensing assemblies on a rotatingreagent carousel over the slide carousel.
 4. A method as claimed inclaim 3 wherein the reagent dispensing assembly and slide carriers aremoved relative to each other by moving both relative to a stationarydispensing station where the reagent metering chamber is compressed. 5.A method as claimed in claim 4 further comprising heating the slides byheating elements on which the slides are supported.
 6. A method asclaimed in claim 1 further comprising heating the slides by heatingelements on which the slides are supported.
 7. A method of performingreactions on a plurality of specimens mounted on microscope slidescomprising:providing a plurality of reagent dispensing assemblies on arotating reagent carousel positioned over a rotating slide carousel,each reagent dispensing assembly comprising:a reagent reservoir; and areagent metering chamber comprising a compressible housing suspendedfrom the reagent reservoir to receive liquid through an inlet from thereservoir and unidirectional check valves at an inlet and an outlet,respectively, of the compressible housing; positioning a plurality ofmicroscope slides on the slide carousel; rotating the reagent carouseland slide carousel relative to each other and relative to a hammer at astationary dispensing station to position a reagent dispensing assemblyover a selected microscope slide at the stationary dispensing station;compressing the reagent metering chamber with the hammer at thedispensing station to eject reagent through the outlet check valve ontothe selected slide; and allowing the reagent metering chamber to revertto its native position due to resiliency of the chamber to draw reagentinto the reagent metering chamber from the reagent reservoir.
 8. Amethod as claimed in claim 7 further comprising heating the slides byheating elements on which the slides are supported.